1-119963373-G-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000256646.7(NOTCH2):c.1915+201C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 152,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Consequence
NOTCH2
ENST00000256646.7 intron
ENST00000256646.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.354
Genes affected
NOTCH2 (HGNC:7882): (notch receptor 2) This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BS2
High AC in GnomAd4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH2 | NM_024408.4 | c.1915+201C>A | intron_variant | ENST00000256646.7 | NP_077719.2 | |||
NOTCH2 | NM_001200001.2 | c.1915+201C>A | intron_variant | NP_001186930.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOTCH2 | ENST00000256646.7 | c.1915+201C>A | intron_variant | 1 | NM_024408.4 | ENSP00000256646.2 | ||||
NOTCH2 | ENST00000479412.2 | n.2053+201C>A | intron_variant | 1 | ||||||
NOTCH2 | ENST00000640021.1 | n.*1039+201C>A | intron_variant | 5 | ENSP00000492223.1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152136Hom.: 0 Cov.: 33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.000118 AC: 18AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74440
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at